title: Genetics of Alzheimer's disease: new evidences for an old hypothesis?
abstract: Alzheimer's disease (AD) is the prime cause of dementia and presents a strong genetic predisposition (60-80% of the attributable risk). In addition to APOE, a major recognized genetic determinant of AD, systematic, high-throughput genomic approaches have recently allowed the characterization of four new genetic determinants: CLU, CR1, PICALM and BIN1. Even if the complete picture of AD genetics is still not fully understood, the characterization of these new AD genetic determinants is probably going to strongly modify our perception of the pathophysiological process involved in AD. The new AD genetic landscape suggests that the common and late-onset forms of the disease are associated with a defect in peripheral Aβ peptide clearance, implying that the amyloid cascade hypothesis could be relevant not only in the AD monogenic forms.
authors.affiliation: INSERM U744, Institut Pasteur de Lille, Université de Lille Nord de France, F-59000 Lille, France. Jean-charles.lambert@pasteur-lille.fr
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics*; D000682:Amyloid / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D051152:Clusterin / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D017463:Receptors, Complement 3b / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid; D001057:Apolipoproteins E; C101410:BIN1 protein, human; C495242:CLU protein, human; C509991:CR1 protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; C439003:PICALM protein, human; D017463:Receptors, Complement 3b; D025521:Tumor Suppressor Proteins